Abstract:
BACKGROUND:Tubulointerstitial fibrosis is a morphologic hallmark of chronic kidney disease and is a key factor in the prediction of progression to end-stage renal failure. Disruption of tubular basement membrane and interstitial extracellular matrix (ECM) via cytokine-induced alterations in matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) may be an important mechanism in this process. The presence of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) and their effects on proximal tubular cells may be critical in this process. METHODS:Human proximal tubular cells were cultured in hormonally defined medium. Cells at 80% confluency were exposed to TNF-alpha (0.1 to 100 ng/mL) or IL-1beta (0.1 to 100 ng/mL) or a combination of both for 48 hours. Activity and expression of MMP-9 was examined by gelatin zymography and Western blot analysis. TIMP-1 expression was analyzed by Western blotting. Signaling through cytokine receptors, protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) pathways was investigated. RESULTS:TNF-alpha but not IL-1beta resulted in a dose-dependent increase in the latent form of MMP-9. TIMP-1 was decreased by treatment with either TNF-alpha or IL-1beta. Cotreatment with IL-1beta abolished the induction of MMP-9 but augmented the inhibition of TIMP-1 in the presence of TNF-alpha. Inhibition of PKC provided evidence of the importance of this pathway in mediating the cytokine-induced suppression of TIMP-1 in human kidney (HK-2) cells. Activation of the extracellular signal-regulated protein kinase (ERK1/2) MAPK mediated the up-regulation of MMP-9 by TNF-alpha whereas p38 was found to be involved in the IL-1beta-mediated inhibition of TNF-alpha-stimulated MMP-9. CONCLUSION:The differential effects of TNF-alpha and IL-1beta on proximal tubular MMP-9 and TIMP-1 expression are mediated through the TNF-RI, the IL-1-RI and the different signaling pathways of PKC, ERK1/2, and p38 MAPK. These findings may provide new insights into the role of proinflammatory cytokines TNF-alpha and IL-1beta in the development and possible therapeutic intervention in tubulointerstitial fibrosis.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Nee LE,McMorrow T,Campbell E,Slattery C,Ryan MPdoi
10.1111/j.1523-1755.2004.00900.xsubject
Has Abstractpub_date
2004-10-01 00:00:00pages
1376-86issue
4eissn
0085-2538issn
1523-1755pii
S0085-2538(15)50204-4journal_volume
66pub_type
杂志文章abstract:BACKGROUND:Among the members of the small leucine-rich proteoglycan family, decorin, biglycan, and fibromodulin have been proposed to be potent modulators of transforming growth factor-beta (TGF-beta) activity, thereby playing an important role in the pathogenesis of fibrotic kidney diseases. Furthermore, decorin expre...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00317.x
更新日期:2000-10-01 00:00:00
abstract::Methods for estimating glomerular volume were compared in Zenker-fixed, paraffin-embedded biopsies from 10 patients with insulin-dependent diabetes mellitus and 6 normal kidney donors. Two methods of measurement of individual glomerular volumes were used: the Cavalieri method (considered the "gold standard") and the m...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.165
更新日期:1992-04-01 00:00:00
abstract::Insulin and growth factors activate the phosphatidylinositide-3-kinase pathway, leading to stimulation of several kinases including serum- and glucocorticoid-inducible kinase isoform SGK3, a transport regulating kinase. Here, we explored the contribution of SGK3 to the regulation of renal tubular phosphate transport. ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.67
更新日期:2011-07-01 00:00:00
abstract:BACKGROUND:Podocyte loss contributes to the development of glomerulosclerosis. Although podocytes have been detected in the urine in certain glomerular diseases, the viability of detached cells is not known. METHODS:Urine was collected from rats with experimental membranous nephropathy [passive Heymann nephritis (PHN)...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00217.x
更新日期:2003-10-01 00:00:00
abstract::We report the first case of a mitochondrial DNA (mtDNA) deletion diagnosed by renal biopsy. An eight-year-old girl with megaloblastic anemia and severe growth retardation developed progressive renal insufficiency accompanied by partial Fanconi syndrome. Histologic examination of the renal biopsy disclosed nonspecific ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.181
更新日期:1994-05-01 00:00:00
abstract::Primary distal renal tubular acidosis is a rare genetic disease. Mutations in SLC4A1, ATP6V0A4, and ATP6V1B1 genes have been described as the cause of the disease, transmitted as either an autosomal dominant or recessive trait. Particular clinical features, such as sensorineural hearing loss, have been mainly describe...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.12.017
更新日期:2017-05-01 00:00:00
abstract::Functional and morphological changes developed rapidly in rats after the intravenous administration of the organic nephrotoxin p-aminophenol. Proximal intratubular pressure remained close to its mean control value of 14.9 +/- 0.9 mm Hg up to 40 min after injection of the nephrotoxin then rose rapidly over the followin...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1983.221
更新日期:1983-12-01 00:00:00
abstract::IgM in the blood of normal individuals consists mainly of 'natural' polyreactive antibodies. Natural IgM is thought to provide an initial defense against infection and to promote the healing of wounded cells. Yet, as Panzer and colleagues show, these benefits can be eclipsed when the IgM binds to damaged cells of the ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2015.153
更新日期:2015-09-01 00:00:00
abstract::The present study was undertaken to evaluate some pathophysiological mechanisms of edema formation in diabetic nephropathy. Sixty-three subjects were investigated: 9 normal subjects (I), 9 normoalbuminuric Type 1 (insulin-dependent) diabetic patients (II), 15 microalbuminuric Type 1 diabetic patients (III), 16 Type 1 ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.332
更新日期:1990-12-01 00:00:00
abstract:BACKGROUND:The long-term prognostic associations of pre- and post-dialysis blood pressures, interdialytic weight gain, and antihypertensive use in hemodialysis patients are unclear. METHODS:The United States Renal Data System (USRDS) Dialysis Morbidity and Mortality Waves 3 and 4 Study, a randomly generated sample of ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00636.x
更新日期:2002-11-01 00:00:00
abstract:BACKGROUND:Crystals of calcium oxalate monohydrate (COM) and excess oxalate ions (OX) stimulate an array of responses inducing localized injury and inflammation in the kidneys. These inflammatory responses are key regulators of development of nephrolithiasis. We propose that monocyte chemoattractant protein-1 (MCP-1), ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00106.x
更新日期:2002-01-01 00:00:00
abstract::From the urine of patients with calcium nephrolithiasis, and of control subjects, we isolated organic substances according to molecular size and tested them for effects on calcium oxalate precipitation. Nine subgroup materials of varying sizes were prepared by ultrafiltration and Sephadex G-200 column chromatography f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1982.33
更新日期:1982-02-01 00:00:00
abstract:BACKGROUND:Gentamicin is commonly used in hemodialysis patients. Gentamicin pharmacokinetics during traditional hemodialysis have been described. Slow daily home (SDH) hemodialysis (7 to 9 hours a day/6 days a week) use is increasing due to benefits observed with increased hemodialysis. We determined gentamicin pharmac...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1046/j.1523-1755.2003.00819.x
更新日期:2003-03-01 00:00:00
abstract::Many transgenic and knockout mice with increased urine flow have structural abnormalities of the renal pelvis and inner medulla. Here, we used high resolution contrast enhanced T1-weighted magnetic resonance imaging of mice whose urea transporters UT-A1 and UT-A3 were deleted (UT-A1/3(-/-) mice) as a model for the in ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.392
更新日期:2008-11-01 00:00:00
abstract::The distribution of precursor nitrogen between urea and glutamine was studied in control and acidotic rats. Acidosis, either acutely induced with hydrochloric acid or chronically induced with ammonium chloride, resulted in a rise in ammonia and a fall in urinary urea excretion; the percent of urinary nitrogen excreted...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1981.182
更新日期:1981-11-01 00:00:00
abstract::One of the challenges of treating patients with glomerulonephritis is to accurately assess disease activity. As renal biopsies are routinely stained for deposits of C3 activation fragments and glomerular C3 deposits are found in most forms of glomerulonephritis, we sought to determine whether a relatively noninvasive ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.332
更新日期:2012-01-01 00:00:00
abstract::Whole-genome microarrays identify large numbers of gene expression changes that appear specifically related to disease states such as antineutrophil cytoplasmic autoantibody (ANCA) and systemic lupus erythematosus. Although understanding this enormous volume of esoteric data is difficult, a few basic concepts regardin...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5002492
更新日期:2007-10-01 00:00:00
abstract::Antibodies against purified rat-kidney-cortex pyruvate carboxylase were raised in rabbits. These polyspecific antibodies recognize pyruvate carboxylase enzymes alone without cross reactivity with other carboxylases as detected by immunoblotting. The abundance of pyruvate carboxylase in the various renal fractions was ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.147
更新日期:1991-06-01 00:00:00
abstract:BACKGROUND:Rats that recover from acute puromycin nephrosis later develop widespread glomerular and tubulointerstitial injury. The current study sought to identify structural changes present in the recovery phase that could precipitate progressive renal disease. METHODS:Stereologic studies were performed 10 weeks afte...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00481.x
更新日期:2002-08-01 00:00:00
abstract::LECT2 amyloidosis is the latest systemic type of amyloidosis to be described. It was discovered in patients with nephrotic syndrome and renal failure and is characterized by amyloid deposition in glomeruli, renal vessels, and interstitium. Clinical and pathological features of earlier phases of this type of amyloidosi...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2010.18
更新日期:2010-05-01 00:00:00
abstract::Cells from RCCT-28A cell line, which exhibited the highest peanut-lectin binding capacity [RCCT-28A(P+)] were separated and cultured attempting to obtain a population of HCO3- secreting cells. The mechanisms of apical solution acid or base extrusion were studied in confluent monolayers. In RCCT-28A (P+) cells net H+ f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.30
更新日期:1993-01-01 00:00:00
abstract::Donor pretreatment of 100 mg/kg each of cyclophosphamide (CY) and methylprednisolone (P) infused 5 hours before nephrectomy invariably prolongs the survival of DLA mismatched, MLC incompatible nonlittermate Beagle renal allografts as well as the survival of mongrel renal allografts. The effect of donor pretreatment ap...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1982.25
更新日期:1982-02-01 00:00:00
abstract:BACKGROUND:This multicenter, open-label, dose-titration study assessed the safety and efficacy of RenaGel(R), a nonabsorbed calcium- and aluminum-free phosphate binder, in lowering serum phosphorus. Secondary outcomes were its effects on serum intact parathyroid hormone (iPTH) and serum lipids. METHODS:Phosphate binde...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1046/j.1523-1755.1999.00240.x
更新日期:1999-01-01 00:00:00
abstract::Sodium depletion has a protective effect on target-organ damage in hypertension independent of blood pressure. Here we tested whether chronic dietary sodium restriction may prevent the development of renal alterations associated with insulin resistance by reducing the inflammatory and oxidant state. Rats were fed norm...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.478
更新日期:2013-04-01 00:00:00
abstract::The following bone density measurements have limited utility in determining bone strength because they do not include bone quality: microarchitecture, mineralization, ability to repair damage, collagen structure, crystal size, or marrow composition. Patients with kidney disease have poor bone quality. Newman et al. no...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2015.11.004
更新日期:2016-01-01 00:00:00
abstract::Antibodies to human leukocyte antigens (HLAs) are a risk factor for acute renal allograft rejection and loss. The role of non-HLAs and their significance to allograft rejection have gained recent attention. Here, we applied protein microarray technology, with the capacity to simultaneously identify 5056 potential anti...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.384
更新日期:2009-12-01 00:00:00
abstract::The high serum fibroblast growth factor 23 (FGF23) levels in patients with acute kidney injury (AKI) and chronic kidney disease (CKD) are associated with increased morbidity and mortality. Mice with folic acid-induced AKI had an increase in bone FGF23 mRNA expression together with an increase in serum FGF23 and severa...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2018.02.026
更新日期:2018-08-01 00:00:00
abstract::Micropuncture studies were carried out in surface nephrons of rats with nephrotoxic-serum (NTS)-induced nephrotic syndrome during a period of active sodium and water retention. It was found that hydrostatic pressure and tubular diameter were increased in the proximal tubules (13.4 +/- 0.2 vs. 10.4 +/- 0.2 mm Hg; 31.3 ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1979.166
更新日期:1979-11-01 00:00:00
abstract::We studied the effect of three antihypertensive drugs on the growth of glomeruli in four- to five-week-old Munich-Wistar rats (N = 24), which were undergoing rapid maturation processes. Young rats were given an angiotensin converting enzyme inhibitor (ACEI, enalapril, 50 mg/liter drinking water), verapamil (50 mg/lite...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.314
更新日期:1990-12-01 00:00:00
abstract:BACKGROUND:Renal inflammation is regulated by a network of local and systemic mediators. Of them, transforming growth factor-beta1 (TGF-beta 1) and glucocorticoids play an important role in deactivating monocytes/macrophages. We examined the hypothesis that TGF-beta 1 effects may be partially achieved through modulatio...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.63.6s.3.x
更新日期:2003-06-01 00:00:00